This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The incomplete digestion of proteins by proteases is a hindrance in their characterization by mass spectrometry. Some proteins are hard to digest due to aggregation. In order to increase the digestion efficiency of proteases we have developed an on-line high pressure digestion system. This system uses UPLC technology to increase the digestion pressure to a maximum of 10,000 psi.